AMFETAMINE SULPHATE Amfetamini sulfas

Amfetamine sulphate EUROPEAN PHARMACOPOEIA 5.0
Flow rate: 1ml/min.
Detection: spectrophotometer at 248 nm.
Injection: 20µl.
Sensitivity: reference solution (a).
Run time: 3 times the retention time of the principal peak in
the chromatogram obtained with the test solution.
System suitability:
— resolution: minimum of 4.0 between the peaks due to
impurity B and ambroxol in the chromatogram obtained
with reference solution (b).
Limits:
— any impurity: not more than the area of the principal
peak in the chromatogram obtained with reference
solution (a) (0.1 per cent),
— total: not more than 3 times the area of the principal peak
in the chromatogram obtained with reference solution (a)
(0.3 per cent),
— disregard limit: 0.1 times the area of the principal peak
in the chromatogram obtained with reference solution (a).
Heavy metals (2.4.8): maximum 20 ppm.
1.0 g complies with limit test C. Prepare the standard using
2mloflead standard solution (10 ppm Pb) R.
Loss on drying (2.2.32): maximum 0.5 per cent, determined
on 1.000 g by drying in an oven at 100-105 °C.
Sulphated ash (2.4.14): maximum 0.1 per cent, determined
on 1.0 g.
ASSAY
Dissolve 0.300 g in 70 ml of alcohol R and add 5 ml of 0.01 M
hydrochloric acid. Carry out a potentiometric titration
(2.2.20), using 0.1 M sodium hydroxide. Readthevolume
added between the two points of inflexion.
1mlof0.1 M sodium hydroxide is equivalent to 41.46 mg of
C 13H 19Br 2ClN 2O.
STORAGE
Store protected from light.
IMPURITIES
A. Ar-CH 2OH: (2-amino-3,5-dibromophenyl)methanol,
B. trans-4-(6,8-dibromo-1,4-dihydroquinazolin-3(2H)yl)cyclohexanol,
C. trans-4-[[(E)-2-amino-3,5-dibromobenzyliden]amino]cyclohexanol,
D. cis-4-[(2-amino-3,5-dibromobenzyl)amino]cyclohexanol,
E. Ar-CH=O: 2-amino-3,5-dibromobenzaldehyde.
AMFETAMINE SULPHATE
Amfetamini sulfas
01/2005:0368
C18H28N2O4S Mr 368.5
DEFINITION
Amfetamine sulphate contains not less than 99.0 per cent
and not more than the equivalent of 100.5 per cent of
bis[(2RS)-1-phenylpropan-2-amine] sulphate, calculated with
reference to the dried substance.
CHARACTERS
A white powder, freely soluble in water, slightly soluble in
alcohol.
IDENTIFICATION
First identification: A, B, E.
Secondidentification:A,C,D,E.
A. The angle of optical rotation (2.2.7) ofsolutionS(see
Tests), measured in a 2 dm tube, is −0.04 to + 0.04.
B. Examine by infrared absorption spectrophotometry
(2.2.24), comparing with the Ph. Eur. reference spectrum
of amfetamine sulphate. Examineasamullinliquid
paraffin R.
C. To 50 ml of solution S add 5 ml of strong sodium
hydroxide solution R and 0.5 ml of benzoyl chloride R
and shake. Continue to add benzoyl chloride R in
portions of 0.5 ml until no further precipitate is formed.
Filter, wash the precipitate with water R and recrystallise
twice from a mixture of equal volumes of alcohol R and
water R and dry at 100 °C to 105 °C. The crystals melt
(2.2.14) at131°Cto135°C.
D. To about 2 mg add 1 ml of sulphuric acid-formaldehyde
reagent R. An orange colour develops and quickly
becomes dark-brown.
E. Solution S gives reaction (a) of sulphates (2.3.1).
TESTS
Solution S. Dissolve 2.0 g in carbon dioxide-free water R
anddiluteto100mlwiththesamesolvent.
Appearance of solution. Solution S is clear (2.2.1) and
colourless (2.2.2, Method II).
Acidity or alkalinity. To25mlofsolutionSadd0.1ml
of methyl red solution R. Notmorethan0.1mlof0.01 M
hydrochloric acid or 0.01 M sodium hydroxide is required
to change the colour of the indicator.
Loss on drying (2.2.32). Not more than 1.0 per cent,
determinedon1.00gbydryinginanovenat100°Cto
105 °C.
Sulphated ash (2.4.14). Not more than 0.1 per cent,
determined on 1.0 g.
966 See the information section on general monographs (cover pages)

EUROPEAN PHARMACOPOEIA 5.0 Amidotrizoic acid dihydrate
ASSAY
Dissolve 0.300 g in 30 ml of anhydrous acetic acid R.Titrate
with 0.1 M perchloric acid, determining the end-point
potentiometrically (2.2.20).
1mlof0.1 M perchloric acid is equivalent to 36.85 mg of
C 18H 28N 2O 4S.
STORAGE
Store protected from light.
01/2005:0873
AMIDOTRIZOIC ACID DIHYDRATE
Acidum amidotrizoicum dihydricum
C 11H 9I 3N 2O 4,2H 2O M r 650
DEFINITION
Amidotrizoic acid dihydrate contains not less than 98.5 per
cent and not more than the equivalent of 101.0 per cent of
3,5-bis(acetylamino)-2,4,6-triiodobenzoic acid, calculated
with reference to the dried substance.
CHARACTERS
A white or almost white, crystalline powder, very slightly
soluble in water and in alcohol. It dissolves in dilute
solutions of alkali hydroxides.
IDENTIFICATION
First identification: A.
Second identification: B, C.
A. Examine by infrared absorption spectrophotometry
(2.2.24), comparing with the spectrum obtained with
amidotrizoic acid dihydrate CRS.
B. Examine the chromatograms obtained in the test for
related substances (see Tests). The principal spot in
the chromatogram obtained with test solution (b) is
similar in position and size to the principal spot in the
chromatogram obtained with reference solution (b).
C. Heat 50 mg gently in a small porcelain dish over a naked
flame. Violet vapour is evolved.
Reference solution (a). Dilute 1 ml of test solution (b) to
50 ml with a 3 per cent V/V solution of ammonia R in
methanol R.
Reference solution (b). Dissolve 50 mg of amidotrizoic acid
dihydrate CRS in a 3 per cent V/V solution of ammonia R
in methanol R and dilute to 10 ml with the same solvent.
Apply separately to the plate 2 µl of each solution. Develop
overapathof15cmusingamixtureof20volumesof
anhydrous formic acid R, 25volumesofmethyl ethyl
ketone R and 60 volumes of toluene R. Allow the plate to dry
until the solvents have evaporated and examine in ultraviolet
lightat254nm.Anyspotinthechromatogramobtained
with test solution (a), apart from the principal spot, is not
more intense than the spot in the chromatogram obtained
with reference solution (a) (0.2 per cent).
Halides. Dissolve 0.55 g in a mixture of 4 ml of dilute
sodium hydroxide solution R and 15 ml of water R. Add
6mlofdilute nitric acid R and filter. 15 ml of the filtrate
complies with the limit test for chlorides (2.4.4) (150 ppm
expressed as chloride).
Free aromatic amines. Maintain the solutions and reagents
in iced water protected from bright light. To 0.50 g in a
50 ml volumetric flask add 15 ml of water R. Shakeand
add 1 ml of dilute sodium hydroxide solution R. Coolin
iced water, add 5 ml of a freshly prepared 5 g/l solution
of sodium nitrite R and 12 ml of dilute hydrochloric
acid R. Shake gently and allow to stand for exactly 2 min
after adding the hydrochloric acid. Add 10 ml of a 20 g/l
solution of ammonium sulphamate R. Allowtostandfor
5 min, shaking frequently, and add 0.15 ml of a 100 g/l
solution of α-naphthol R in alcohol R. Shakeandallowto
stand for 5 min. Add 3.5 ml of buffer solution pH 10.9 R,
mix and dilute to 50.0 ml with water R. Theabsorbance
(2.2.25), measured within 20 min at 485 nm using as the
compensation liquid a solution prepared at the same time
and in the same manner but omitting the substance to be
examined, is not greater than 0.30.
Heavy metals (2.4.8). Dissolve 2.0 g in 4 ml of dilute sodium
hydroxide solution R and dilute to 20 ml with water R.
12 ml of this solution complies with limit test A for heavy
metals (20 ppm). Prepare the standard using lead standard
solution (2 ppm Pb) R.
Loss on drying (2.2.32):4.5percentto7.0percent,
determined on 0.500 g by drying in an oven at 100 °C to
105 °C.
Sulphated ash (2.4.14). Not more than 0.1 per cent,
determined on 1.0 g.
TESTS
ASSAY
To 0.150 g in a 250 ml round-bottomed flask add 5 ml of
strong sodium hydroxide solution R, 20mlofwater R,
1gofzinc powder R and a few glass beads. Boil under a
reflux condenser for 30 min. Allow to cool and rinse the
condenser with 20 ml of water R, adding the rinsings to
Appearance of solution. Dissolve 1.0 g in dilute sodium the flask. Filter through a sintered-glass filter and wash the
hydroxide solution R and dilute to 20 ml with the same filter with several quantities of water R. Collectthefiltrate
solvent. The solution is clear (2.2.1) andcolourless(2.2.2, and washings. Add 40 ml of dilute sulphuric acid R and
Method II).
titrate immediately with 0.1 M silver nitrate. Determine
Related substances. Examine by thin-layer chromatography
(2.2.27), using silica gel GF254 R as the coating substance.
Test solution (a). Dissolve 0.50 g of the substance to be
examined in a 3 per cent V/V solution of ammonia R in
the end-point potentiometrically (2.2.20), using a suitable
electrode system such as silver-mercurous sulphate.
1mlof0.1 M silver nitrate is equivalent to 20.47 mg of
C11H9I3N2O4. methanol R and dilute to 10 ml with the same solvent.
Test solution (b). Dilute 1 ml of test solution (a) to 10 ml
STORAGE
with a 3 per cent V/V solution of ammonia R in methanol R. Store protected from light.
GeneralNotices(1)applytoallmonographsandothertexts 967